ABSTRACT I This is an application for a Mentored Quantitative Research Development Award for Dr. Yue Xuan, a biomedical research scientist at the University of California, San Francisco. Dr. Xuan is establishing herself as a young investigator in patient-oriented research of aortic valve replacement. This K25 award will provide Dr. Xuan with the support necessary to accomplish the following goals: (1) to focus on clinical investigation of the thrombosis after transcatheter valve-in-valve implantation; (2) to acquire training in radiology and identify the risk factors of thrombosis by incorporating the clinical data and patient-specific computational modeling; and to (3) integrate her biomechanical expertise to answer clinical questions in the treatment of cardiovascular diseases. While Dr. Xuan has a solid background in computational modeling, she is much less so in the other important disciplines named above. To achieve these goals, Dr. Xuan has assembled a mentoring team comprised of a primary mentor, Dr. Elaine Tseng, Professor of Surgery at UCSF and Chief of Cardiothoracic Surgery in San Francisco Veterans Affairs Medical Center, co-mentor, Dr. Liang Ge, an Assistant Adjunct professor in UCSF, who has expertise in computational modeling of ascending aortic aneurysm and aortic valve disease, and co- mentor Dr. Danny Dvir, international leader in valve-in-valve therapies and valve degeneration and an interventional cardiologist in University of Washington. Dr. Xuan will also work closely with Dr. Kendrick Shunk and Jeffery Zimmet, interventional cardiologist in UCSF and San Francisco VA Medical Center, to understand the clinical questions of the valve-in-valve procedure. The mentoring team also includes Dr. Michael Hope, associate professor in UCSF and Chief of radiology in San Francisco VA Medical Center and Dr. David Saloner, professor in Radiology at UCSF and international leader in cardiovascular MRI, who will supervise and direct the medical imaging and MRI study. Dr. Xuan has developed structured training plan incorporating of didactic training, formal coursework, besides multidisciplinary mentorship in clinical study, medical imaging and patient- specific computational modeling. Transcatheter aortic valve-in-valve (VIV) implantation stands to revolutionize the treatment of aortic valve disease after a failed surgical bioprosthetic valve. The proposed study will incorporate both the clinical imaging, clinical follow-up data and patient-specific computational simulation to address the most urgent questions for the thrombosis after VIV. We expect the outcomes of these studies will fill critical knowledge gaps in thrombosis formation from the hemodynamics perspective, improve clinical management of thrombosis, and significantly improve the future clinical outcome through patient-specific risk prediction. This research will form the basis for an in-depth study of thrombosis and bioprosthetic valve failure in the VIV procedure, to be proposed in an R01 grant application before the end of the proposed project.